OICC Press Journal of Nanostructure in Chemistry 2193-8865 12 1 (February 2022) 2021 04 09 Effect of thymoquinone-loaded lipid–polymer nanoparticles as an oral delivery system on anticancer efficiency of doxorubicin 10.1007/s40097-021-00398-6 EN Faezeh Abbaspour Moghaddam School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, IR Mahboubeh Ebrahimian School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, IR Fatemeh Oroojalian Department of Advanced Sciences and Technologies, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, IR Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, IR Rezvan Yazdian-Robati Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, IR Fatemeh Kalalinia Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, IR Lobat Tayebi Marquette University School of Dentistry, Milwaukee, WI, 53233, US Maryam Hashemi Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, IR Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, IR Journal Article 2021 04 09 Abstract In this study, thymoquinone (TQ) was encapsulated into lipid–polymer nanoparticles (LPNPs) consisting of phosphatidylcholine (PC) and poly lactide–co-glycolide (PLGA) to enhance anticancer and oral delivery efficiency of TQ. We also co-delivered TQ nanoparticles with free doxorubicin (DOX) to increase DOX efficiency. Single emulsion solvent evaporation method was exploited to prepare PLGA-TQ and PLGA-PC-TQ NPs. The physicochemical properties of synthetized NPs and their cellular uptake across Caco-2 cells were assessed. Cytotoxicity of different formulations of TQ and their co-delivery with free DOX were determined by MTT assay on colon cancer cell lines (C26). Cell migration was also evaluated by wound healing migration assay. LPNPs containing TQ with an average diameter of 184 nm and 60% loading efficiency showed more release at simulated intestinal fluid pH of 6.8 compared to polymeric NPs. At an acidic pH, however, the release of TQ from PLGA-PC was about 2% after 120 h. The cytotoxicity studies indicated that PLGA-PC-TQ NPs improved anticancer activity of DOX more than TQ NPs. Uptake of PLGA-PC-TQ through the Caco-2 cells was 2.5 times greater compared to NPs without PC. PLGA-PC-TQ NPs also exhibited significantly greater reduction of cancer cell migration. The results demonstrate that co-delivery of PLGA-PC encapsulated TQ through oral administration and free DOX could improve anticancer efficiency of DOX.